1. Field of the Invention
This invention relates to a new class of polyanhydrides.
2. Background Information
Various polyanhydrides are known in the art as described in the references discussed in the Description of Related Art given hereinafter. Some of these have been used for the controlled release of agents such as drugs, e.g. poly [bis (p-carboxyphenoxy) alkane anhydrides], and copolyanhydrides of bis (p-carboxyphenoxy) alkanes with sebacic acid. However, a disadvantage of some of these known polyanhydrides is their uneven rate of hydrolytic cleavage at different temperatures, with substantially higher rates of cleavage occurring at temperatures above 0.degree. C. than at 0.degree. C. or below. A possible cause of this lack of uniformity of hydrolytic cleavage of known polyanhydrides which can be formed into polymer matrices suitable for controlled release of a drug or other agent, is the nature of the repeating units making up the polymers which are derived from the monomer or monomers used to prepare the polymer. Thus, both terminal groups of at least some of the repeating units making up all or most of the known polyanhydrides used for the controlled release of drugs or other functional substances, are hydrophilic anhydride linkages randomly linked to hydrophobic anhydride linkages attached to aromatic ring carbon atoms. The hydrophilic anhydride linkages are easily cleaved by hydrolysis and thus cause phase separation. At least in some cases, this is believed to cause a too rapid rate of hydrolytic cleavage at storage temperatures above 0.degree. C.
3. Description of Related Art
The following prior art references are disclosed in accordance with the terms of 37 CFR 1.56, 1.97 and 1.98.
K. W. Leong et al., "Synthesis of Polyanhydrides: Melt-Polycondensation, Dehydrochlorination and Dehydrative Coupling" published in Macromolecules, 20(4), 705-712, (April, 1987), disclose a variety of polyanhydrides including terephthalic homopolyanhydrides of bis (carboxyphenoxy) alkanes, terephthalic acid, sebacic acid and glutaric acid, and copolyanhydrides of bis (carboxyphenoxy) alkanes with sebacic acid, and terephthalic acid with adipic or sebacic acid.
K. W. Leong et al, "Polyanhydrides for Controlled Release of Bioactive Agents," published in Biomaterials 1986, Vol. 7, September, 364-371, disclose the use of homopolyanhydrides of bis (carboxyphenoxy) alkanes and terephthalic acid, and copolyanhydrides of each of the latter dicarboxylic acids with sebacic acid, as controlled release agents for drugs in the form of polymer matrices containing the drug.
U.S. Pat. No. 4,546,152, issued October 8, 1985 to Koelmel et al., discloses the dimethyl ester of 4-carboxymethoxybenzoic acid, the corresponding 1,2 and 1,3-isomers, and the corresponding diacids. Cited in the specification of this patent is U.S. Pat. No. 4,510,295 issued to Bezwada et al, which discloses polymers, apparently polyesters, derived from 4-(carboxymethoxy) benzoic acid and glycolide and/or lactide.
Kito et al., Kogyo Kagaku Zasshi 1971, 74(11), 2313-15 (abstracted in C.A. 76(9): 45892c, 1972) teach the preparation of omega (p-carboxyphenoxy) alkanoic acids and their methyl esters.
Shamilov et al., Deposited Doctoral Dissertation SPSTL Khp-D82, 6 pages (1982) (abstracted in C.A. 101(3): 23072t) teach the synthesis and study of derivatives of 4-carboxy-1-phenoxyacetic acid.